P1318: THE IMPACT OF MELPHALAN DOSING IN COMBINATION WITH FLUDARABINE IN CLINICAL OUTCOMES OF PATIENTS WITH ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROMES RECEIVING ALLO-HCT
Authors: O. Albanyan, D. Kalos, J. Kim, R. Faramand, H. Elmariah, A. Mishra, T. Nishihori, L. Perez, M. Nieder, J. Pidala, N. Bejnayan
Journal: HemaSphere (2022)

Background: Allogenic hematopoietic cell transplant (allo-HCT) is the only curative treatment option for many adults with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Fludarabine (Flu) and melphalan (Mel) reduced intensity conditioning (RIC) regimen is frequently used for older patients and those with comorbidities. Mel dosing based on body surface area raised concerns for patient under- or overdosing in prior report. Aims: Here we studied the impact of Mel dose per kilogram of actual body weight (mg/kg) on clinical outcomes of allo-HCT. Methods: We retrospectively evaluated patients with AML or MDS who underwent allo-HCT from an 8/8 HLA matched donor and received Flu/Mel (Mel dose of 100-140 mg/m2). The objectives were to compare overall survival (OS), relapsed free survival (RFS), non-relapse mortality (NRM), relapse, grade II-IV acute graft vs host disease (aGVHD), chronic GVHD (cGVHD), mucositis and gastrointestinal (GI) toxicity based on Mel mg/kg dosing. We calculated the median Mel mg/kg dose and compared the outcomes of patients receiving median and above versus below median dose. Results: From January 2008 to December 2020, 345 patients underwent allo-HCT with Flu/Mel, all patients received peripheral blood graft, 209 patients transplanted for AML and 136 for MDS. Patient characteristics are presented in Table 1. Median dose of Mel was 3.28 mg/kg (range, 1.61-6.21 mg/kg);173 patients received Mel ≥ 3.28 mg/kg and 172 patients received Mel < 3.28 mg/kg. Median follow up time for the entire study cohort was 36.5 months. For the Mel ≥ 3.28 mg/kg vs. Mel < 3.28 mg/kg groups, median OS was 57.5 months (95% CI: 39.5 – N.E) vs. 46.6 months (95% CI: 28.2 – 109.5, p=0.49) and median RFS was 51.4 months (95% CI: 30.7 – 70.4) vs. 29.7 months (95% CI: 18.1 – 98.0, p=0.36). Similarly, there were no significant differences between the Mel ≥ 3.28 mg/kg and Mel < 3.28 mg/kg groups in 2-year rates of relapse (19.9% vs. 23.8%, p=0.3) and NRM (20.9% vs. 25.4%, p=0.94; Figure 1D). The cumulative incidences of day 100 grade II-IV aGVHD (39.9% vs. 39.0%, p=0.86), grade III-IV aGVHD (9.2% and 9.3%, p=0.99) and moderate/severe cGVHD (67.6% vs.58.4%, p=0.19) were also similar for patients receiving Mel ≥ 3.28 mg/kg vs. Mel < 3.28 mg/kg. On multivariable analysis, the Mel dose/kg had no independent impact on OS, RFS, relapse, NRM, acute and chronic GVHD outcomes. OS was worse with KPS ≤ 80 (HR, 1.51, p=0.014) and HCT-CI ≤ 3 (HR, 1.68, p=0.004), while RFS was worse with KPS ≤ 80 (HR, 1.5, p=0.012), HCT-CI ≥ 3 (HR, 1.72, p=0.002) and high/very high DRI (HR, 1.36, p=0.046). KPS ≤ 80 (HR1.75, p=0.006) and HCT-CI ≥ 3 (HR,1.67, p=0.023) were also associated with higher NRM. Cumulative incidence of any grade mucositis for Mel ≥ 3.28 mg/kg vs. Mel < 3.28 mg/kg was 33.5% vs. 29.1% (p=0.37) and of grade III mucositis was 12.1% vs. 24.0%. None of the study patients experienced grade IV mucositis. Incidence of GI toxicity with non-infectious diarrhea following Flu/Mel chemotherapy of any grade was 65.3% vs. 60.5%, (p=0.35) and of grade III was 16.8% vs. 19.2% for patients received Mel ≥ 3.28 mg/kg vs. Mel < 3.28 mg/kg, respectively. We observed no grade IV GI toxicity on our study patients. Image:Summary/Conclusion: Our study showed no significate influence of Mel mg/kg dose on clinical outcomes of allo-HCT in patients with AML and MDS receiving Flu/Mel RIC. Similarly, mucositis and GI toxicities were not affected by the Mel mg/kg dose. These findings support Mel dosing based on body surface area when combined with Flu as RIC regimen used for allo-HCT.